Predictors of incident stroke among individuals without coronary artery calcification: A pooled cohort analysis from the Multi-Ethnic Study of Atherosclerosis, Jackson Heart Study, and Framingham Heart Study

Introduction: The absence of coronary artery calcium (CAC = 0) is associated with low risk of stroke events; however, predictors of incident stroke among those with CAC = 0 are not known. Methods: Individual participant-level data were pooled from three prospective cohorts (Multi-Ethnic Study of Atherosclerosis [MESA], Jackson Heart Study, and Framingham Heart Study). Multivariable-adjusted Cox proportional hazards models were used to study the association between cardiovascular risk factors and incident adjudicated stroke among individuals with CAC = 0 who were free of clinical atherosclerotic cardiovascular disease at baseline. Results: Among 6180 participants (mean age 53 [SD 11] years, 62% women, and 44% White, 36% Black, and 20% other individuals), over a median (IQR) follow up of 15 (12–16) years, there were 122 strokes (95 ischemic, 27 hemorrhagic) with an overall unadjusted event rate of 2.0 per 1000 person-years. After multivariable adjustment, risk factors associated with overall stroke included (hazard ratio [95% CI]) systolic blood pressure (SBP): 1.19 (1.05–1.36) per 10-mmHg increase and carotid intima–media thickness (CIMT): 1.21 (1.04–1.42) per 0.1-mm increment. Current cigarette smoking: 2.68 (1.11–6.50), SBP: 1.23 (1.06–1.42) per 10-mmHg increase, and CIMT: 1.25 (1.04–1.49) per 0.1-mm increment were associated with ischemic stroke, whereas C-reactive protein was associated with hemorrhagic stroke risk (0.49, 0.25–0.93). Conclusion: In a large cohort of individuals with CAC = 0, the rate for incident stroke was low (2.0 per 1000-person years) and was associated with modifiable risk factors.